The results of the proposed studies will provide a better understanding of the biology and immunology of Toxoplasma gondii, the epidemiology, diagnosis and treatment of acute and chronic congenital and acquired toxoplasmosis, and the unique role of Toxoplasma in infection in the immunologically compromised host. Studies will continue on isolation and characterization of cell membrane antigens of T. gondii using our monoclonal antibodies. Presently available diagnostic procedures will be improved and new ones developed including improved detection of antigen in serum and other body fluids, increasing the sensitivity of the IgM-ELISA test, determining the reliability of demonstrating Toxoplasma in brain biopsy material using our newly developed PAP technique, and further characterization of the histopathology and role of antigen deposits in the lymphadenopathic form. The antigens present in human serum will be isolated and characterized. The cell type harboring circulating Toxoplasma in patients with parasitemia will be determined and the dynamics of endogenous reinfection will be studied in the normal and immunosuppressed host. The role of the lymphocyte-macrophage system in resistance to Toxoplasma will be studied, including: the nature of the lymphocyte response to Toxoplasma, suppression of specific lymphocyte recognition of Toxoplasma and activation of macrophages during acute human toxoplasmosis, the specificity of macrophage recognition of Toxoplasma, and the mechanism whereby Toxoplasma are inhibited or killed by phagocytic cells. The efficacy of newer antimicrobials and their synergistic effects will be evaluated in animal models.